A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis
| العنوان: | A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis |
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| المؤلفون: | Gregory Swan, Jia Geng, Eunchong Park, Quanquan Ding, John Zhou, Ciana Walcott, Junyi J. Zhang, Hsin-I Huang, Gianna Elena Hammer, Donghai Wang |
| المصدر: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Chemokine, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, T cell, Immunology, Protein Prenylation, T cells, Biology, Mice, Chemokine receptor, Immune system, Heterotrimeric G protein, medicine, Animals, Immunology and Allergy, lymphocyte migration, Original Research, protein geranylgeranylation, autoimmunity, Correction, FOXP3, Cell Differentiation, RC581-607, Acquired immune system, adaptive immune response, Cell biology, body regions, Chemotaxis, Leukocyte, medicine.anatomical_structure, biology.protein, Th17 Cells, Receptors, Chemokine, Lipid modification, Immunologic diseases. Allergy, Signal Transduction |
| الوصف: | Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro. Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3+ regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea78181d227cbc9959a1725f0a99d1c9Test https://www.frontiersin.org/articles/10.3389/fimmu.2021.641188/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ea78181d227cbc9959a1725f0a99d1c9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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